After a missed dose of methotrexate, don't take two doses together. The US Trexall label says to call your healthcare provider about your next dose. The NHS says you can take it the next day or the day after, and to call if it's more than 2 days late.
A missed week is usually not an emergency. A 2021 modeling study found that for a typical rheumatoid arthritis patient already settled on treatment, a single missed dose did not drop methotrexate's active form below the level linked to its effect. Its analysis suggests that missing individual doses "should not be an immediate cause for concern." The bigger risk is the opposite mistake: taking extra to catch up.
This guide covers once-weekly methotrexate for conditions like rheumatoid arthritis and psoriasis. If you take methotrexate for cancer, your schedule may be different, so ask your cancer care team.
This article provides general information about medication management and is not a substitute for professional medical advice. Consult your doctor or pharmacist for advice specific to your medications.
Took an extra dose, or took it two days in a row? That is a different problem. The Trexall leaflet says that if you take too much, call your healthcare provider or go to the nearest hospital emergency room right away. Then read what to do if you took methotrexate two days in a row.
Can I Take Methotrexate a Day Late? Three Official Answers
Three official sources give three answers.
| Source | Written for | What it says about a missed dose |
|---|---|---|
| US Trexall label (Patient Information) | Patients in the US | "If you miss taking a dose of TREXALL, call your healthcare provider for instructions about when to take your next dose of TREXALL." |
| NHS methotrexate page | Patients in the UK | Take it "the next day or the day after." If it is "more than 2 days late, contact your doctor or the clinic." |
| NHS Specialist Pharmacy Service | Pharmacists and other clinicians in the UK | "Take the dose if it is remembered on the next day or the day after." "If the dose is 3 or more days late, skip the forgotten dose entirely, and take the next dose as scheduled on the usual day." |
Sources: Trexall label, NHS, NHS Specialist Pharmacy Service.
In the US, the label says to call. The UK windows show how one health system handles it, but your prescriber may set a different plan. They see your regular blood tests, and the label notes that methotrexate's half-life "increases with the severity of renal impairment."
Can You Take Methotrexate Twice in One Week to Catch Up?
Not unless your prescriber tells you to. On this point the three sources line up. The NHS says: "Never take 2 doses together to make up for a missed dose." The Specialist Pharmacy Service says the same, and the Trexall leaflet says: "Do not take more TREXALL than prescribed."
The reason is in the Trexall boxed warning: "Methotrexate tablets when inadvertently administered once daily have resulted in death." The label says the deadly errors most often involved people "taking TREXALL daily when a weekly dosing regimen was prescribed." The Otrexup label adds that toxic effects "may be related in frequency and severity to dose or frequency of administration but have been seen at all doses."
The Specialist Pharmacy Service gives an example. If your day is Tuesday, a missed dose can go on Wednesday or Thursday, and "the next dose can be taken as usual, on the following Tuesday." Past Thursday, its advice to clinicians is to skip. Either way, the late dose stays at least five days from the next one.
The urge to double up can be strong when your joints hurt. A 2018 review of methotrexate errors describes a man whose arthritis got worse, so he doubled his weekly dose on his own. He also had kidney problems and took medicines that interact with methotrexate. He was in the hospital within a week and died. The doubled dose was one of several things that went wrong.
Missed Your Methotrexate Injection?
The US labels for two methotrexate auto-injectors, Otrexup and Rasuvo, do not give a missed-dose instruction. What they stress is the schedule. The Otrexup leaflet says: "Inject Otrexup only 1 time each week." The Rasuvo label advises picking "an appropriate fixed day of the week for the injection." If you're not sure the shot went in, the Otrexup and Rasuvo leaflets say: "do not inject another dose. Call your pharmacist or doctor right away."
For a missed dose of methotrexate injection, call the clinic or nurse who trained you. Ask whether this week's shot is still on, and which day the next one goes. The model in the next two sections used tablet data, not injections.
What Happens If You Miss a Week of Methotrexate?
For a typical patient on steady treatment, a missed weekly dose of methotrexate matters less than you might fear. In your blood, methotrexate drops fast: the Trexall label puts its half-life at "approximately 3 to 10 hours." But it adds that "small amounts of methotrexate polyglutamates may remain in tissues for extended periods."
A 2021 modeling study in Open Access Rheumatology explains that these polyglutamates build up in red blood cells, where they are used as a marker of how well the drug is working. The authors used that build-up to estimate what missed tablets do. For the typical rheumatoid arthritis patient:
- It took about 6 weeks to reach the level linked to methotrexate working, and about 22 weeks to level off.
- After about 10 weeks of treatment, a single missed dose did not push levels below that working range.
- At a steady level, stopping completely dropped levels below that range in about 3 weeks.
Two cautions. This was a computer model, and the authors call its findings "a hypothesis that requires testing in prospective studies." And people vary: "for some patients, the therapeutic effect could be lost after missing a single dose." Early on, a miss can also slow things down: in the model, it delayed reaching the working level by a week or two.
In a US study that tracked pill bottles electronically, 60 people with rheumatoid arthritis took their weekly methotrexate correctly in 75% of weeks over 24 weeks.
What If You Miss 2 Doses of Methotrexate or More?
In the same model, once the drug was working, two missed weeks in a row did not cost the modeled patient the effect. Three in a row did. The authors wrote that runs of 3 or more missed doses "are typically expected to result in a loss of the therapeutic effect."
In a 2018 study in Annals of the Rheumatic Diseases, 316 people with rheumatoid arthritis got a flu shot, and about half paused methotrexate for 2 weeks on purpose. Average disease activity barely moved. But 10.6% of the pause group flared within 4 weeks, versus 5.1% of those who kept taking it, a gap that was not statistically significant. The authors report that "all patients with a flare returned to their baseline disease activity when MTX was resumed."
That was a planned pause in people whose disease was calm. If you have missed two or more weeks, call your prescriber before your next dose.
Feeling Worse After a Missed Methotrexate Dose?
A sore, stiff morning after a missed dose feels like proof. It may not be the missed dose.
- Treatment may not have kicked in yet. The Trexall label says most rheumatoid arthritis responses came "between 3 and 6 weeks" after starting, and some took "up to 12 weeks."
- Flares happen anyway. In the 2018 trial above, 5.1% of people who never paused still flared within 4 weeks.
- It could be an infection. Methotrexate can raise your risk of infections, and the Trexall leaflet says to tell your provider "right away if you develop a new fever or if you have any symptoms of infection." The NHS lists a high temperature, muscle aches and a sore throat as possible signs.
Either way, tell your prescriber how you feel.
Should You Skip Methotrexate When You're Sick?
That is your prescriber's call, and it is best made before you skip. The Trexall label tells prescribers to "withhold or discontinue methotrexate tablets for serious infections," weighing how serious your condition is. The NHS tells patients to "ask your doctor for urgent advice if you get an infection, such as COVID-19, or if you've been in contact with anyone who has chickenpox or shingles."
The same goes for vaccines: tell your provider about any you have coming up. The Trexall leaflet says "you should not receive live vaccines during treatment." If your doctor plans a skip, ask when to restart. A forgotten dose has no plan yet, which is why the call matters. For your other medicines, see which medications to stop when you're sick.
How to Stop Missing Your Weekly Methotrexate Day
A weekly dose has no daily habit to hang on, so it slips. A few things help:
- Use one fixed day. The NHS says to take it "on the same day each week." A medication safety review even advises prescribers to avoid Monday, "because this might be misread as 'morning.'"
- Store it away from your daily pills. The NHS says to "store your weekly methotrexate separately, away from any other medicines that you take daily."
- Watch the weekend. In Pillo's data from 60,000 users, Saturday is the day people put off medication most. Here's why weekends are hard.
- If you can't remember whether you took it, don't take another dose to be safe. Ask your pharmacist, and see what to do when you can't remember if you took your medication.
Pillo can help with the weekly part. Set methotrexate for one day a week, and the persistent alarm keeps going until you respond. Your dose history shows whether this week's dose is logged. A dose note can hold what your clinic told you, like "took it Thursday, next dose Tuesday." If you manage a parent's methotrexate, Dependents Management puts their schedule in your own app, free for up to two dependents. Pillo is free for unlimited medications, with ads.
Other weekly drugs have their own rules, like the Fosamax catch-up rule. For daily medicines, start with what to do if you missed a dose of medication.
FAQ
Can I take methotrexate a day late?
The NHS says yes, "the next day or the day after," and to call if it is more than 2 days late. The US Trexall label says to call your provider about your next dose. Under either rule, never take two doses together.
Can I take methotrexate a day early?
Ask your pharmacist before you do. Taking it early shortens the gap since your last dose. A US study that tracked methotrexate doses electronically counted "doses taken at an interval shorter than prescribed" as early dosing, separate from correct dosing.
What if I can't remember whether I took my methotrexate this week?
Don't take another dose just in case. The Trexall label warns that taking it "more often than prescribed, can lead to severe side effects and cause death." Ask your provider or pharmacist what to do this week.
Does missing one dose of methotrexate cause side effects?
The main worry with a missed dose is your condition creeping back: stiffness, pain or skin symptoms. A 2021 modeling study suggests one missed week usually doesn't drop drug levels below the range linked to its effect in rheumatoid arthritis on steady treatment, though some people are more sensitive.
What about my folic acid if my methotrexate is late?
Folic acid is often prescribed alongside methotrexate, and a late methotrexate dose can land on your folic acid day. Ask your pharmacist how to line the two up this week.
